transforming-growth-factor-beta and Erectile-Dysfunction

The correlation between hypoxia and erectile dysfunction (ED) has been universally acknowledged for decades in the academic world. The phenotypic modulation of corpus cavernosum smooth muscle cells (CCSMCs) is regarded as one of the factors of hypoxia-induced ED, but the underlying mechanisms remain unclear. Recent researches show some correlation between autophagy and phenotypic modulation of CCSMCs, which may be associated with the overexpressions of PDGF, TGF-β, and vasoactive factors in the organism following hypoxia.. 缺氧与勃起功能障碍（ED）的相关性在学术界已被公认数十年之久，阴茎海绵体平滑肌细胞（CCSMC）表型的转换目前被认为是缺氧并发ED的机制之一，但关于表型转化更深一步机制尚不明确。最近的研究发现，细胞自噬与平滑肌的表型转化有着一定的相关性，而缺氧后机体内血小板源性生长因子(PDGF)、转化生长因子β(TGF-β)、 血管活性因子等物质的过表达可能是两者之间的联系点。.

Topics: Animals; Autophagy; Erectile Dysfunction; Humans; Hypoxia; Male; Muscle, Smooth; Myocytes, Smooth Muscle; Penis; Transforming Growth Factor beta

Recent advances in the research on erectile dysfunction (ED) has more clearly explained the mechanism of penile erection, which is a hemodynamic process involving relaxation of corpus cavernosum smooth muscle and related arterials, and NO-cGMP signaling pathway proven to play an important role on modulating the relaxation of corpus cavernosum smooth muscle. Studies on NOS and PDEs not only provide strong evidence for the clinical treatment of ED, but also provide the chance to develop Sildenafil. Although the gene therapy for ED is still in the laboratory stage by now, it may be one of the effective clinical therapies for ED in future.

Topics: Cyclic GMP; Erectile Dysfunction; Genetic Therapy; Humans; Male; Nitric Oxide; Penile Erection; Transforming Growth Factor beta; Transforming Growth Factor beta1

During erection, oxygen tension changes in the corpus cavernosum penis from 25-40 mm Hg in the flaccid state to 90-100 mm Hg in the erect state. The relationship between corpus cavernosum trabecular structure and erectile function is dependent on a critical balance of smooth muscle to connective tissue for successful veno-occlusion. In this article, the potential role for transforming growth factor beta(1) (TGF-beta(1)) and prostaglandin E (PGE) in maintaining a functional smooth muscle/connective tissue balance are discussed as well as the importance of oxygen tension in the synthesis of these factors. Correlations between animal models of disease as well as clinical reports are presented in support of a role for hypoxemia in penile fibrosis. A case is presented for a biological basis of nocturnal penile tumescence in the preservation of potency and an overall hypothesis for the molecular pathology of erectile dysfunction is proposed.

Topics: Animals; Erectile Dysfunction; Fibrosis; Humans; Hypoxia; Male; Muscle, Smooth; Penis; Prostaglandins E; Transforming Growth Factor beta

The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in anterior lumbar interbody fusion (ALIF) is controversial regarding the reported complication rates and cost. The authors aimed to assess the complication rates of performing ALIF using rhBMP-2.. This is a prospective study of consecutive patients who underwent ALIF performed by a single spine surgeon and a single vascular surgeon between 2009 and 2012. All patients underwent placement of a polyetheretherketone (PEEK) cage filled with rhBMP-2 and a separate anterior titanium plate. Preoperative clinical data, operative details, postoperative complications, and clinical and radiographic outcomes were recorded for all patients. Clinical outcome measures included back and leg pain visual analog scale scores, Oswestry Disability Index (ODI), and SF-36 Physical and Mental Component Summary (PCS and MCS) scores. Radiographic assessment of fusion was performed using high-definition CT scanning. Male patients were screened pre- and postoperatively regarding sexual dysfunction, specifically retrograde ejaculation (RE).. The study comprised 131 patients with a mean age of 45.3 years. There were 67 men (51.1%) and 64 women (48.9%). Of the 131 patients, 117 (89.3%) underwent ALIF at L5-S1, 9 (6.9%) at L4-5, and 5 (3.8%) at both L4-5 and L5-S1. The overall complication rate was 19.1% (25 of 131), with 17 patients (13.0%) experiencing minor complications and 8 (6.1%) experiencing major complications. The mean estimated blood loss per ALIF level was 115 ml. There was 1 incidence (1.5%) of RE. No significant vascular injuries occurred. No prosthesis failure occurred with the PEEK cage and separate anterior screw-plate. Back and leg pain improved 57.2% and 61.8%, respectively. The ODI improved 54.3%, with PCS and MCS scores improving 41.7% and 21.3%, respectively. Solid interbody fusion was observed in 96.9% of patients at 12 months.. Anterior lumbar interbody fusion with a vascular access surgeon and spine surgeon, using a separate cage and anterior screw-plate, provides a very robust and reliable construct with low complication rates, high fusion rates, and positive clinical outcomes, and it is cost-effective. The authors did not experience the high rates of RE reported by other authors using rhBMP-2.

Topics: Adult; Aged; Benzophenones; Bone Morphogenetic Protein 2; Bone Plates; Bone Screws; Ejaculation; Erectile Dysfunction; Female; Humans; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Ketones; Low Back Pain; Lumbar Vertebrae; Male; Middle Aged; Polyethylene Glycols; Polymers; Prospective Studies; Recombinant Proteins; Sacrum; Spinal Fusion; Titanium; Transforming Growth Factor beta; Treatment Outcome; Young Adult

To investigate whether Leech-Centipede (LC) Granules can improve erectile function in rats with diabetes mellitus-associated erectile dysfunction (DMED) through endothelial-to-mesenchymal transition (EndMT) inhibition.. Components of LC Granules were identified via ultra-high-performance liquid chromatography. Thirty male Sprague Dawley rats were injected with streptozotocin and fed continuously for 8 weeks to establish the DMED rat model. Rats with erectile dysfunction symptoms diagnosed using apomorphine were divided into DMED and low-, medium-, and high-doses LC groups (n=6 in each). The negative control (NC, n=6) and DMED groups were given 5 mL of deionized water via intragastric gavage, and the low-, medium- and the high-doses LC groups were administered LC at 1.6, 3.2, and 6.4 g/kg, respectively, via intragastric gavage for 4 weeks. The intracavernous pressure (ICP), mean arterial pressure (MAP), and nitric oxide (NO) levels in cavernous tissue were measured for each group. Quantitative reverse transcription-polymerase chain reaction and Western blot were used to detect mRNA and protein expressions of endothelial and mesenchymal markers. Immunofluorescence staining was used to observe α-SMA, and Masson's trichrome staining was performed to determine the myofiber/collagen ratio.. A total of 474 active components were identified. After treatment, the ICP/MAP value and NO level were significantly higher in the medium- and high-dose LC groups than in the DMED group (P<0.05). Compared with the DMED groups, the medium- and high-dose groups LC significantly increased and decreased endothelial and mesenchymal markers expression, respectively (P<0.05). Tumor growth factor (TGF)β R II, p-Smad2, and p-Smad3 levels were considerably higher following diabetes onset but reduced following LC intervention (P<0.05), except for TGF β 1 (P>0.05). α-SMA expression was significantly higher in the DMED group and was reduced in all LC intervention groups (P>0.05). The myofiber/collagen ratio in the LC groups was higher than that in the DMED group but lower than that in the NC group (all P<0.05).. LC Granules may improve the erectile function of DMED rats by suppressing TGF-β/Smad pathway to reverse EndMT.

Topics: Animals; Chilopoda; Diabetes Mellitus, Experimental; Erectile Dysfunction; Humans; Male; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta

The main pathophysiologic conditions of erectile dysfunction (ED) after radical prostatectomy are considered to be corporal fibrosis and apoptosis induced by cavernosal nerve (CN) injury.. In a rat model of CN crush injury (CNCI), we investigated whether combination treatment with JNK inhibitor (JNKi), SP600125, and HDAC inhibitor (HDACi), suberoylanilide-hydroxamic-7 acid (SAHA), for 2 weeks after CNCI would restore erectile function by suppressing fibrosis and apoptosis through normalization of JNK and HDAC pathways.. Seventy 12-week-old rats were randomly divided into five groups: Sham surgery, CNCI alone, CNCI treated with daily intraperitoneal injection of 10 mg/kg JNKi, CNCI treated with daily oral administration of 25.0 mg/kg HDACi, and CNCI daily treated with a combination. Two weeks after CNCI, we investigated the erectile response to electrostimulation and conducted histological staining, caspase-3 activity assay, and western blot analysis.. CNCI alone resulted in significantly reduced intracavernosal pressure/mean arterial pressure (MAP) and area under the curve/MAP, decreased smooth muscle (SM)/collagen ratio and SM content, higher caspase-3 activity, and increased protein levels of total HDAC3, transforming growth factor (TGF)-β, fibronectin, and c-Jun phosphorylation, compared with the Sham surgery. The CNCI groups exposed to JNKi, HDACi or both showed improvements in erectile-responses and SM/collagen ratio, compared to the CNCI alone. The combined treatment showed additional improvement in erectile responses at 1.0V stimulation and in SM/collagen ratio compared to the single agent treatment. SM content, caspase-3 activity, and c-Jun phosphorylation improved in the two CNCI groups exposed to JNKi. The two CNCI groups exposed to HDACi showed normalization of protein levels of HDAC3, fibronectin, and TGF-β.. The combined administration of JNKi and HDACi during the acute phase after CNCI in rats can preserve ED by suppressing cavernosal fibrosis and apoptosis by normalizing the HDAC/TGF-β and JNK pathways.

Topics: Animals; Caspase 3; Disease Models, Animal; Erectile Dysfunction; Fibronectins; Fibrosis; Histone Deacetylase Inhibitors; Humans; Male; MAP Kinase Signaling System; Penile Erection; Penis; Phosphorylation; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta; Vorinostat

A Erectile dysfunction (ED) is one of the well-known comorbidities in males with diabetes mellitus (DM), whose pathogenesis might be induced by dysregulation of corpus cavernosum smooth muscle cells. UC-MSCs are multipotent cells that attract considerable interest due to immunoregulatory properties and might be a potential strategy to regulate and recover the functional cells and tissues, including tissue improvement in DMED.. This study aims to determine the efficacy of UC-MSCs in improving the erectile function of DMED rats through analyzing the expression of TGF-β, α-SMA, and collagen.. Total number of 30 male Sprague-Dawley rats (6 to 8 weeks old) were randomly divided into four groups (negative control group, positive control group, T1 group, and T2 group). After 16 h fast, 24 rats were randomly selected and intraperitoneally injected with streptozotocin to induce DM. At 8 weeks after STZ injection, rats with DMED were identified by unresponsive erectile stimulation within 30 min. PC group received 500 μL; T1 rats treated with 500 μL PBS containing 1x106 UC-MSCs; T2 rats treated with 500 μL PBS containing 3x106 UC-MSCs. After MSCs treatment, the rats were sacrificed and the corpus cavernosum tissues were prepared for histological observations.. This study resulted in the administration of UC-MSCs could downregulate the expression of TGF-β, α-SMA, and collagen leading to the improvement of DMED.. UC-MSCs improve the expression of TGF-β, α-SMA, and collagen on erectile dysfunction in streptozotocin-induced diabetic rats.

Topics: Animals; Collagen; Diabetes Mellitus, Experimental; Erectile Dysfunction; Male; Mesenchymal Stem Cells; Rats; Rats, Sprague-Dawley; Streptozocin; Transforming Growth Factor beta; Umbilical Cord

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia, which causes endothelial dysfunction and peripheral neuropathy, ultimately leading to multiple complications. One prevalent complication is diabetic erectile dysfunction (ED), which is more severe and more resistant to treatment than nondiabetic ED. The serum glycoprotein leucine-rich ɑ-2-glycoprotein 1 (LRG1) is a modulator of TGF-β-mediated angiogenesis and has been proposed as a biomarker for a variety of diseases, including DM. Here, we found that the adhesion GPCR latrophilin-2 (LPHN2) is a TGF-β-independent receptor of LRG1. By interacting with LPHN2, LRG1 promotes both angiogenic and neurotrophic processes in mouse tissue explants under hyperglycemic conditions. Preclinical studies in a diabetic ED mouse model showed that LRG1 administration into the penile tissue, which exhibits significantly increased LPHN2 expression, fully restores erectile function by rescuing vascular and neurological abnormalities. Further investigations revealed that PI3K, AKT, and NF-κB p65 constitute the key intracellular signaling pathway of the LRG1/LPHN2 axis, providing important mechanistic insights into LRG1-mediated angiogenesis and nerve regeneration in DM. Our findings suggest that LRG1 can be a potential new therapeutic option for treating aberrant peripheral blood vessels and neuropathy associated with diabetic complications, such as diabetic ED.

Topics: Animals; Diabetes Mellitus; Erectile Dysfunction; Glycoproteins; Humans; Male; Mice; Neovascularization, Pathologic; Receptors, Peptide; Receptors, Transforming Growth Factor beta; Transforming Growth Factor beta

Topics: Adipose Tissue; Adult; Aged; Blood Vessels; Cell Differentiation; Cellular Senescence; Epidermal Growth Factor; ErbB Receptors; Erectile Dysfunction; Gene Expression Regulation, Developmental; Genome, Human; Humans; Male; Mesenchymal Stem Cells; Middle Aged; Penis; Receptors, Androgen; Receptors, Antigen, T-Cell; RNA, Messenger; Signal Transduction; Stromal Cells; Tissue Array Analysis; Transforming Growth Factor beta

Sildenafil is a potent and selective inhibitor of phosphodiesterase-5 (PDE5) and is considered first-line therapy for erectile dysfunction. Nowadays, Sildenafil is used extensively throughout the world on patients with pulmonary hypertension. However, few studies have evaluated the possible side effects of chronic Sildenafil treatment on the male reproductive system, specifically in the prostate. In the present study, it was demonstrated via morphological and ultrastructural analysis that chronic treatment with Sildenafil induced an enhancement of the glandular activity of the prostate. In addition, mice treated with Sildenafil showed a significant increase in testosterone serum levels. However, no statistically significant differences were observed in nitric oxide serum levels, or in sGC, eNOS, PSA and TGF-β prostatic expression. In conclusion, the present study suggests that chronic use of Sildenafil does not cause evident prostatic damage, and therefore, can be used pharmacologically to treat a variety of disorders.

Topics: Animals; Erectile Dysfunction; Humans; Hypertension, Pulmonary; Male; Mice; Mice, Inbred C57BL; Nitric Oxide; Nitric Oxide Synthase Type III; Piperazines; Prostate; Prostate-Specific Antigen; Purines; Sildenafil Citrate; Sulfonamides; Testosterone; Transforming Growth Factor beta

Topics: Bone Morphogenetic Protein 2; Erectile Dysfunction; Female; Humans; Low Back Pain; Lumbar Vertebrae; Male; Recombinant Proteins; Spinal Fusion; Transforming Growth Factor beta

The seriousness of metabolic syndrome is not due to the disease itself but its promotion of other diseases, such as erectile dysfunction and cardiovascular and cerebrovascular diseases. We investigated the effects of Korean red ginseng (KRG, Panax ginseng) extract on erectile function in a rat model of metabolic syndrome. We divided the rats into three groups: control, metabolic syndrome+normal saline (N/S) and metabolic syndrome+KRG. To determine the occurrence of metabolic syndrome in all groups, body weight and various biochemical parameters (e.g., blood glucose, insulin, cholesterol) were measured, and the intra-abdominal glucose tolerance test was performed. To investigate penile erection, the peak intracavernosal pressure (ICP), mean arterial pressure (MAP) and Masson's trichrome stain were evaluated. Erectile function was also investigated by measuring the cyclic guanosine monophosphate (cGMP) levels of the corpus cavernosum. We found that the various biochemical parameters and body weight were similar in the metabolic syndrome+KRG group and the control group, although the values were slightly higher. The peak ICP/MAP ratio of the metabolic syndrome+N/S group was markedly decreased compared to the other groups. The cGMP level of the corpus cavernosum in the metabolic syndrome+N/S group was significantly lower than that of the other groups. As demonstrated in this model of metabolic syndrome with erectile dysfunction, KRG may improve erectile function.

Topics: Animals; Arterial Pressure; Cyclic GMP; Disease Models, Animal; Erectile Dysfunction; Male; Metabolic Syndrome; Panax; Penile Erection; Penis; Phytotherapy; Plant Extracts; Rats; Rats, Inbred WKY; Transforming Growth Factor beta

Neurogenic erectile dysfunction remains a serious complication in the postprostatectomy population. Effective protective and regenerative neuromodulatory strategies are needed.. To determine the effect of growth differentiation factor-5 (GDF-5) on erectile function and its mechanism in a rat model of cavernous nerve (CN) injury.. Erectile function was assessed by CN electrostimulation at 4 weeks. Penile tissues were examined by real-time polymerase chain reaction (PCR) and immunohistochemical analyses.. Forty-eight male Sprague-Dawley rats were randomly divided into six equal groups: one group underwent sham operation (uninjured controls), while five groups underwent bilateral CN crush. Crush-injury groups were treated at the time of injury with intracavernous injection of a slow-release suspension of liquid microparticles containing no GDF-5 (vehicle), 0.4 microg (low concentration), 2 microg (intermediate concentration), or 10 microg GDF-5 (high concentration). One untreated group served as injured controls.. GDF-5 enhanced erectile recovery and significantly increased intracavernous pressure in the low and intermediate-concentration groups vs. injured controls. Low-concentration GDF-5 demonstrated the best functional preservation, as the intracavernous pressure increase in this group did not differ significantly from uninjured controls. A dose-response relationship was confirmed for the effects of GDF-5 in penile tissue. Low-concentration GDF-5 showed better preservation of the penile dorsal nerves and antiapoptotic effects in the corpus cavernosum (P < 0.05 vs. injured controls). Although high concentration GDF-5 did not confer meaningful erectile recovery, this dose was more effective at decreasing transforming growth factor-beta than low-concentration GDF-5.. Intracavernous injection of low (0.4 microg) or intermediate-concentration GDF-5 (2 microg) was effective in preserving erectile function in a rat model of neurogenic erectile dysfunction. The underlying mechanism appears to involve neuron preservation and antiapoptosis.

Topics: Animals; Apoptosis; Blood Pressure; Disease Models, Animal; Dose-Response Relationship, Drug; Erectile Dysfunction; Gene Expression; Growth Differentiation Factor 5; In Situ Nick-End Labeling; Injections; Male; Nerve Crush; Nitric Oxide Synthase; Penile Erection; Penis; Peripheral Nerve Injuries; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transforming Growth Factor beta

Transforming growth factor (TGF) beta1 has been suggested to have an important role in cavernous fibrosis and resultant erectile dysfunction. For further elucidation of TGFbeta1 signaling in association with cavernous fibrosis, we developed a rat model of cavernous fibrosis using TGFbeta1-producing NIH 3T3 fibroblasts (NIH 3T3-TGFbeta1). The NIH 3T3-TGFbeta1 cells were injected into male Sprague-Dawley rats intracavernously. Masson trichrome staining at 20 days postinjection showed multiple fibrous scars in the rats injected with the NIH 3T3-TGFbeta1 cells (group 3), whereas no histological evidence of cavernous fibrosis was found in the control rats (group 1) or the recombinant human TGFbeta1 protein-injected rats (group 2). Immunohistochemical staining revealed a higher expression of TGFbeta1 and its type II receptor in group 3 than in groups 1 and 2. Electrostimulation of the cavernous nerve revealed that the maximal intracavernous pressure was significantly lower in group 3 than in groups 1 and 2 (P < 0.01). The expression of transgenic TGFbeta1 mRNA continued to 10 days after injection of the cells. The NIH 3T3-TGFbeta1 cells sufficiently induced relatively long-lasting cavernous fibrosis. This novel animal model may contribute to future investigations of the pathogenesis of penile fibrosis associated with TGFbeta1 signaling and the development of new therapeutics targeting this pathway.

Topics: Animals; Cell Transplantation; Disease Models, Animal; Erectile Dysfunction; Fibrosis; Gene Expression; Male; Mice; NIH 3T3 Cells; Penile Diseases; Penile Erection; Rats; Rats, Sprague-Dawley; Signal Transduction; Transforming Growth Factor beta; Transforming Growth Factor beta1

It has been hypothesized that transforming growth factor-beta1 (TGF-beta1) signalling is involved in erectile dysfunction (ED). This study was undertaken to elucidate in detail whether expression of TGF-beta1 and its type II receptor is clinically related to various causes of ED. Fifty-four patients with ED and 24 potent men were the subjects of this study. After multidisciplinary work-up, the ED was classified as psychogenic (n = 6), neurogenic (n = 15), or vasculogenic (n = 33). In every subject, percutaneous cavernous biopsy was performed using a Biopty gun. Masson's trichrome staining was used to quantitate collagen fibres and immunohistochemical staining to evaluate both TGF-beta1 and its type II receptor by scoring the intensity of immunoreactivity (score 0-6). Collagen fibres were significantly more abundant in men with vasculogenic ED (72.7 +/- 17.7%) than in control subjects (43.3 +/- 11.2%) or those with psychogenic (45.0 +/- 12.2%) or neurogenic (51.3 +/- 20.3%) ED (p < 0.01). Expression of TGF-beta1 was significantly greater in vasculogenic ED (4.3 +/- 1.3) than in the control subjects (2.4 +/- 0.9) or psychogenic ED (2.0 +/- 0.6) groups (p < 0.01). Type II receptor expression was also significantly increased in vasculogenic ED (3.9 +/- 1.3) compared with control (2.2 +/- 0.7) and psychogenic (2.2 +/- 0.8) or neurogenic (2.6 +/- 1.3) ED (p < 0.01). Of the ED groups, both the hyperlipidaemia and the atherosclerosis patients showed significantly more fibrosis than those without the condition (p < 0.05). The abundance of collagen fibres correlated well with both TGF-beta1 expression (gamma = 0.81; p < 0.001) and receptor II expression (gamma = 0.83; p < 0.001). These results suggest that TGF-beta1 and its receptor II pathway are involved in cavernous fibrosis and ED in man. Patients with vascular risk factors such as hyperlipidaemia and atherosclerosis are liable to ED by activation of this pathway.

Topics: Adult; Aged; Case-Control Studies; Erectile Dysfunction; Gene Expression Regulation; Humans; Male; Middle Aged; Penis; Protein Serine-Threonine Kinases; Receptor, Transforming Growth Factor-beta Type II; Receptors, Transforming Growth Factor beta; Risk Factors; Transforming Growth Factor beta; Transforming Growth Factor beta1

To explore the expression of transforming growth factor-beta(1) (TGF-beta1) in penile tissue from rats after bilateral cavernosal nerve (CN) ablation, mimicking patients who have had no nerve-sparing during prostatectomy.. Ten adult male rats (neurectomy group) had a bilateral CN resection aseptically under an operating microscope, with six sham-operated rats as controls. Fifteen weeks after surgery an apomorphine test was used in all rats to assess penile erection. The penile specimens were then collected and prepared for detecting the expression of TGF-beta1 by reverse transcription-polymerase chain reaction (RT-PCR), western blot and immunohistochemistry, and for quantitative analysis of the ratio of smooth muscle to collagen fibres in the corpus cavernosum with confocal microscopy.. All rats in the sham-operated group but none after neurectomy had an erectile response after subcutaneous injection with apomorphine (100 micro g/kg). Immunohistochemistry, RT-PCR and western blot analyses showed a significantly higher expression of TGF-beta1 in the penile tissues after neurectomy than after sham surgery. Smooth muscle cells (fluorescing red) and collagen fibres (green autofluorescence) after paraformaldehyde fixation, were clearly identified by confocal microscopy. The fluorescence intensity expressed as the mean (sem) ratio of smooth muscle to collagen fibres in the corpus cavernosum after neurectomy was 0.265 (0.125), significantly lower than that in the sham-operated group, at 0.760 (0.196) (P < 0.01).. An increased expression of TGF-beta1 in penile tissue which promotes the synthesis of collagen may be one of the important factors for the erectile dysfunction caused by bilateral CN ablation. Similar pathophysiological processes may occur in the corpus cavernosum of patients after radical prostatectomy.

Topics: Animals; Blotting, Western; Erectile Dysfunction; Immunohistochemistry; Male; Muscle, Smooth; Penis; Prostatectomy; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA; Transforming Growth Factor beta; Transforming Growth Factor beta1

To evaluate the plasma TGF-beta1 level in erectile dysfunction (ED) patients of various causes.. Sixty-two patients with ED and 26 potent men were subjected to the study. Based on multidisciplinary work-ups, including medical history, physical examinations, blood tests with lipid profile and hormones, penile duplex Doppler ultrasonogram and neurophysiological tests, causes for ED were classified as psychogenic (n=15), neurogenic (n=16) and vasculogenic (n=31). The plasma TGF-beta1 level was measured by the ELISA method.. The plasma TGF-beta1 level was significantly increased in the ED group (6.7+/-4.9 ng/mL), compared to the control (4.0 +/-2.1 ng/mL) (P<0.01). In the ED groups, there was a significant increase in the vasculogenic group (9.0 +/-5.5 ng/mL), compared to the psychogenic (3.8 +/-1.8 ng/mL) and neurogenic groups (4.8+/-3.2 ng/mL) (P<0.01). Of the vascular risk factors, both the smoking (7.5 +/-4.7 ng/mL) and dyslipidemia groups (7.4+/-4.4 ng/mL) showed significantly increased plasma TGF-beta1 levels, compared to the non-smokers (5.5+/-2.8 ng/mL), and those without dyslipidemia (4.8+/-2.8 ng/mL) (P<0.05).. Vascular risk factors are associated with an elevated plasma TGF-beta1 level, which may contribute to cavernous fibrosis and ED.

Topics: Adult; Aged; Arteriosclerosis; Diabetes Mellitus; Enzyme-Linked Immunosorbent Assay; Erectile Dysfunction; Female; Humans; Hyperlipidemias; Hypertension; Impotence, Vasculogenic; Male; Middle Aged; Penis; Risk Factors; Smoking; Transforming Growth Factor beta; Transforming Growth Factor beta1; Ultrasonography

The molecular mechanisms of erectile dysfunction with aging are unclear. Recent studies have suggested that growth factors may play a role in the etiology of erectile dysfunction. This present study was designed to test the hypothesis that gene expression of various growth factors such as TGF alpha, TGF beta 1, TGF beta 2, TGF beta 3, IGF and NGF modulate with aging in rat penile tissues. For this purpose, total RNA was extracted from young and old rat penile tissues and the gene expression for these growth factors was determined by differential reverse-transcriptase-polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. mRNA levels of growth factors were quantified by using beta-actin as an internal standard. The results of these experiments suggest that: (1) young and old rat penile tissues expressed mRNA transcripts for TGF alpha, TGF beta 1, TGF beta 2, TGF beta 3, IGF and NGF; (2) TGF beta 1 gene expression was significantly increased in old rat penile tissues as compared to young; (3) mRNA transcripts for NGF and TGF beta 3 were significantly lower in old rat penile tissues as compared to young; and (4) TGF alpha, TGF beta 2 and IGF mRNA expression did not change in young and old rat penile tissues. These results suggest that the differential gene expression for various growth factors in young and old rat penile tissues may be important in understanding the pathophysiology of erectile dysfunction associated with aging.

Topics: Aging; Animals; Erectile Dysfunction; Gene Expression; Growth Substances; Male; Nerve Growth Factors; Penis; Polymerase Chain Reaction; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Somatomedins; Transforming Growth Factor alpha; Transforming Growth Factor beta